Growth rate-dependent global effects on gene expression in bacteria.

Bacterial gene expression depends not only on specific regulatory mechanisms, but also on bacterial growth, because important global parameters such as the abundance of RNA polymerases and ribosomes are all growth-rate dependent. Understanding of these global effects is necessary for a quantitative understanding of gene regulation and for the design of synthetic genetic circuits. We find that the observed growth-rate dependence of constitutive gene expression can be explained by a simple model using the measured growth-rate dependence of the relevant cellular parameters. More complex growth dependencies for genetic circuits involving activators, repressors, and feedback control were analyzed and verified experimentally with synthetic circuits. Additional results suggest a feedback mechanism mediated by general growth-dependent effects that does not require explicit gene regulation if the expressed protein affects cell growth. This mechanism can lead to growth bistability and promote the acquisition of important physiological functions such as antibiotic resistance and tolerance (persistence). Copyright 2009 Elsevier Inc. All rights reserved.